New research from Melbourne scientists shows that raising stress hormone levels in male parental mice leads to a predisposition to anxiety and depression-related disorders in the next two generations of offspring.
Led by Professor Anthony Hannan of the Florey Institute of Neuroscience and Mental Health, the team have identified a molecular pathway that could transmit environmental signals received by the fathers down to their children and grandchildren.
Epigenetics is an emerging area of interest in biological research. It is the bridge between ‘nurture’ and ‘nature’, providing the signals that switch certain genes on or off in response to our environment. The exciting aspect of this work is that it provides, for the first time, a mechanism whereby these environmental signals, inducing stress hormone elevation, can be passed on to descendants.
The researchers, Dr Terence Pang and Dr Annabel Short, increased stress hormone levels in male mice and then measured the behavior of the first and second generations of offspring. Both generations had changes in anxiety and depression-related behaviors.
Until now, the signal that might be responsible for such behaviours being passed down generations has remained a mystery, but Prof Hannan and his group have identified three possible candidate molecules. These molecules are called ‘microRNAs’, and they act to switch genes on or off.
One gene they are known to regulate is IGF2, and when the researchers looked in the brains of the offspring mice, levels of this gene were indeed altered compared to offspring from non-stressed parents or grandparents.
The work strongly suggests the urgent need for large scale observational studies of human populations. Professor Hannan said, “There is evidence that the children of Holocaust survivors have epigenetic changes that they inherited from their parents. This was a small study of 32 families, which needs to be followed up – for example by looking at epigenetic effects on children of people suffering post traumatic stress disorder from car accidents or war experiences.
“This work is difficult to perform in humans however as it’s hard to separate the environment that the children were reared in from the genetic component inherited from their parents, except in adoption studies. The fact we have identified for the first time a molecular pathway that could be the causative agent in ‘inheriting’ experiences from a father you’ve never met really shows the power of doing these studies in closely related animal models.”
There could be major public health and socio-economic implications from the team’s findings, which seeks to minimise the risk of future generations developing anxiety, depression and other stress-related mental health disorders.
At the moment, health advice around conception mainly focuses on healthy lifestyle and diet in women. This new works emphasises the need to also optimise the father’s environment in order to positively influence his child’s health outcomes.
The open access research was published in the journal Translational Psychiatry (Nature Publishing Group), is freely available to view [PDF]
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